YC-1 potentiates the nitric oxide/cyclic GMP pathway in corpus cavernosum and facilitates penile erection in rats
YC-1 potentiates the nitric oxide/cyclic GMP pathway in corpus cavernosum and facilitates penile erection in rats
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DOI：
10.1016/s0014-2999(02)02730-9
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发表时间：
2003-01-01
影响因子：
5
通讯作者：
Brioni, JD
中科院分区：
文献类型：
--
作者：
Hsieh, GC;O'Neill, AB;Brioni, JD
本研究的目的是表征YC-1（3-（5 '-羟甲基-2'-呋喃基）-1-苄基吲唑），一种可溶性鸟苷酸环化酶激活剂，在体外和体内的药理作用，对海绵体平滑肌和阴茎勃起活动。YC-1使苯肾上腺素预收缩的海绵体平滑肌松弛（EC_（50）=4.4 μ M），这种作用可被1H-[1，2，4]恶二唑[4，3-a]喹喔啉-1-酮（ODQ）部分拮抗。ODQ是一种选择性可溶性鸟苷酸环化酶抑制剂，完全阻断硝普钠诱导的舒张，表明YC-1与可溶性鸟苷酸环化酶结合的位点与一氧化氮（NO）不同。YC-1和硝普钠，但不是西地那非（1-100 μ M）引起浓度依赖性增加环GMP水平在培养的兔海绵体平滑肌细胞，并产生协同效应。腹腔注射YC-1（10 μ mol/kg）诱发大鼠阴茎勃起，发生率为70%。更重要的是，YC-1能够显著增强次优剂量阿扑吗啡的促勃起作用。这些结果表明，可溶性鸟苷酸环化酶激活剂YC-1增加环GMP水平，导致海绵体平滑肌松弛。这些生化事件可能与YC-1在体内的促勃起特性有关。(C)2002 Elsevier Science B. V.保留所有权利。
The aim of present study was to characterize the in vitro and in vivo pharmacological effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1benzyl indazole), a soluble guanylate cyclase activator, on corpus cavernosal smooth muscle and penile erectile activity. YC-1 relaxed phenylephrine precontracted cavernosal smooth muscle (EC50=4.4 muM) and this effect was partially antagonized by 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ). ODQ is a selective soluble guanylate cyclase inhibitor that completely blocked the relaxation induced by sodium nitroprusside, suggesting that YC-1 binds to soluble guanylate cyclase at a different site from nitric oxide (NO). Both YC-1 and sodium nitroprusside, but not sildenafil (1-100 muM) caused concentration-dependent increases in cyclic GMP levels in cultured rabbit cavemosal smooth muscle cells and produced synergistic effects. Intraperitoneal administration of YC-1 (10 mumol/kg) evoked penile erection in rats with 70% incidence. More importantly, YC-1 was able to significantly augment the pro-erectile effects of a suboptimal dose of apomorphine. These results suggest that the soluble guanylate cyclase activator YC-1 increases cyclic GMP levels, leading to relaxation of cavemosal smooth muscle. These biochemical events may be related to the pro-erectile properties of YC-1 in vivo. (C) 2002 Elsevier Science B.V. All rights reserved.